Biphenylic types of organic compounds in accordance with our invention or which can be prepared from those compounds can be used as a medicament, or more preferably for the manufacture of a medicament for treatment of hypertension and may function as angiotensin II antagonists. Most of molecules from this group consist of cyclic, preferably heterocyclic part connected through —CH2— bridge to the 4-biphenylyl part in which the distant phenyl ring is further orto substituted with a polar substituent. Some well known representatives of this group like losartan, irbesartan, candesartan, olmesartan and valsartan include a tetrazole as a polar substituent while telmisartan includes a carboxylic group in this part of molecule. Also compounds being substituted by other polar substituents, which include oxo or dioxo substituted imidazoles, thiazoles, oxazoles or pyrimidines may be used as a medicament or can be used in the process of manufacturing of a medicament.
2′-substituted (such as tetrazolyl but also formyl and hydroxymethyl) 4-biphenylyl substituted molecules, may be useful angiotenzin II antagonists. Furthermore the enzymes in human body can transform these into a carboxylic moiety. Molecules, which include such fragments are therefore potential prodrugs with improved pharmacokinetics. For instance telmisartan, which has a 2′ carboxylic acid substituent, is poorly soluble in water or physiological fluids and there is a tendency to find an (alternative) optimal way to ensure a good bioavailability.
In EP 682021 a 4′-((1,4′-dimethyl-2′-propyl-2,6′-bi(1H-benzo[d]imidazol)-1′-yl)methyl)biphenyl-2-carbaldehyde is used for condensation reaction with thiazolidin-2,4-dion. In EP 520423 various 2-formyl derivatives are used in cyanohydrine reaction in a preparation of 2,4 dioxotiazidinyl substituted compounds. Such formyl derivatives were prepared from corresponding carboxy derivatives of already finished molecular systems by two step procedure, first reducing carboxy group to hydroxymethyl with further oxidation to a formyl derivative. It is more convenient to make a conversion into the formyl group in the early synthetic step.